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Purity: ≥98%
PHT-7.3 is a novel, potent and selective inhibitor of connector enhancer of kinase suppressor of Ras 1 (Cnk1) which is a pleckstrin homology (PH) domain-containing scaffold protein that increases the efficiency of Ras signaling pathways, imparting efficiency and specificity to the response of cell proliferation, survival, and migration. PHT-7.3 inhibited mut-KRas, but not wild-type KRas cancer cell and tumor growth and signaling. Thus, the PH domain of Cnk1 is a druggable target whose inhibition selectively blocks mutant KRas activation, making Cnk1 an attractive therapeutic target in patients with mut-KRAS-driven cancer. These findings identify a therapeutic strategy to selectively block oncogenic KRas activity through the PH domain of Cnk1, which reduces its cell membrane binding, decreasing the efficiency of Ras signaling and tumor growth.
| ln Vivo |
Mut-KRas(G12S) A549 xenografts and mut-KRasG12V H441 xenografts show cytostatic antitumor activity in response to PHT-7.3 (200 mg/kg; i.p.; daily; for 20 days) [1].
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| Animal Protocol |
Animal/Disease Models: Female NOD-SCID (severe combined immunodeficient) mouse (mut-KRas A549 NSCLC xenograft, mut-KRas H441 NSCLC xenograft) [1]
Doses: 200 mg/kg Route of Administration: intraperitoneal (ip) injection, daily, for 20 days Experimental Results: In mut-KRas(G12S) A549 xenografts and mut-KRasG12V H441 xenografts. |
| References |
| Molecular Formula |
C24H23N3O3S
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|---|---|
| Molecular Weight |
433.52272439003
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| Exact Mass |
433.146
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| CAS # |
1614225-93-2
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| PubChem CID |
76287542
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
3.7
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
31
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| Complexity |
661
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C=C(C2C=CC(C)=CC=2)N=C1CN1C(C2C=CC=CC=2C(CC2OCCCO2)=N1)=O
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| InChi Key |
AFPMVLVIYVAFSP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H23N3O3S/c1-16-7-9-17(10-8-16)21-15-31-22(25-21)14-27-24(28)19-6-3-2-5-18(19)20(26-27)13-23-29-11-4-12-30-23/h2-3,5-10,15,23H,4,11-14H2,1H3
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| Chemical Name |
4-(1,3-dioxan-2-ylmethyl)-2-[[4-(4-methylphenyl)-1,3-thiazol-2-yl]methyl]phthalazin-1-one
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~62.5 mg/mL (~144.17 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (14.42 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 6.25 mg/mL (14.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3067 mL | 11.5335 mL | 23.0670 mL | |
| 5 mM | 0.4613 mL | 2.3067 mL | 4.6134 mL | |
| 10 mM | 0.2307 mL | 1.1533 mL | 2.3067 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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